The underlying molecular mechanism of oral cancer invasion is not apparent. In this review, we explain the molecular mechanism for the epithelial-mesenchymal transition （EMT） and EMT-related cell migration and invasion by TGF-β in human oral squamous cell carcinoma （hOSCC）cells. We examined whether TGF-β-induced EMT of hOSCC cells, and cell migration and invasive potential. Among six kinds of hOSCC cells, HSC-4 cells responded to TGF-β1 the most from the upregulations of Smad2 phosphorylation and the expression of target genes against TGF-β. The expression of Slug, which is an EMT-related transcription factor, was increased by TGF-β1 stimulation. The expression suppression of Slug by RNA interference inhibited the expression of the mesenchymal marker and the cell migration of the HSC-4 cells. The expressions of binding proteins for integrin α3β1, which activates the focal adhesion kinase （FAK） to relay signals for the promotion of migratory activity, were increased by TGF-β1 stimulation. Thus, EMT and cell migration through the integrin α3β1/FAK pathway were upregulated by TGF-β1-induced Slug.

On the other hand, the expression of matrix metalloproteinase-10 （MMP-10） was increased by TGF-β1 stimulation, and the invasive potential was inhibited by MMP-10 siRNA. Slug siRNA suppressed the expression of MMP-10, indicating that the invasion of HSC-4 cells was induced through Slug-dependent upregulation of MMP-10 expression by TGF-β1 stimulation. In addition, Slug siRNA suppressed Wnt-5b expression. Wnt-5b stimulation upregulated MMP-10 expression in HSC-4 cells. Moreover, Wnt-5b siRNA suppressed invasive potential and MMP-10 expression in HSC-4 cells.

Consequently, TGF-β1 induced the migratory activity and invasive ability of hOSCCs by Slug/α3β1/FAK and Slug/Wnt-5b/MMP-10 signal transduction systems, respectively.